Dichloro-dialkylamino-methanes



United States Patent 3,146,268 DICHLORO-DIALKYLAMENO-METHANES Ernst Jenny, Basel, Switzerland, assignor to Ciba Limited, Basel, Switzerland N0 Drawing. Original application Aug. 19, 1957, Ser.

No. 679,073, now Patent No. 2,995,565, dated Aug. 8, 1961. Divided and this application Aug. 20, 1959, Ser. No. 834,942 Claims priority, application, Switzerland, Aug. 27, 1956, 36,364; July 18, 1957, 48,560 3 Claims. (Cl. 260-583) This application is a divisional of application Serial No. 679,073, now Patent 2,995,565.

The present invention relates to new products, more particularly to dichloro-di(lower)alkylamino methanes of the general formula These compounds are new, and can be made by treating a dialkylformamide with phosgene. A dialkyl-formamide containing lower alkyl groups, such as diethylformamide or especially di-methylformamide, is advantageously used.

The treatment of the dialkylformamide with phosgene is advantageously carried out in an anhydrous inert organic solvent. Good results are obtained for example, with halogenated hydrocarbons such as monochlorobenzene, dichlorobenzene, tetrachlorethane, chloroform and especially carbon tetrachloride as solvents. When phosgene is introduced into such a solution of a dialkylformamide, the reaction takes place Very easily. It is of advantage to work at about room temperature or a somewhat lower temperature, for example, within the range of C. to 20 C.

It may be assumed that an addition product of phosgene and the dialkylformamide is formed in a first stage, and that from this product carbon dioxide is split off in a subsequent stage. Disregarding the intermediate addition product, the reaction may be represented as follows:

alkyl\ 11 01 alkyl Cl /N =0 O=( J NJJH C0 alkyl All alkyl 1 Accordingly 1 mol of carbon dioxide is liberated by the reaction of 1 mol of the dialkylformamide with 1 mol of phosgene, and this has been verified experimentally.

When the reaction is complete, the reaction mixture consists almost wholly of the solvent and the dichloro- (dialkylamino)-methane, which is generally suspended in the solvent. To obtain a dichloro-(dialkylamino)-methane which is sufficiently pure for most purposes, the solvent merely has to be distilled from the mixture as soon as the reaction has been completed.

The said dichloro-di(lower)alkylamino methanes are especially useful for the manufacture of cyclic aldehydes. For this purpose a cyclic compound containing a reactive hydrogen atom bound to a carbon atom is: condensed with a dichloro-(dialkylarnino)-methane with the splitting oh. of one molecule of hydrogen chloride, and the condensation product so obtained is treated with a hydrolysing agent.

The cyclic compound containing a reactive hydrogen atom, which is used as starting material, may, for example, belong to the aromatic, alicyclic or heterocyclic series. There is advantageously used a tertiary aminoaryl compound containing a reactive hydrogen atom, especially a free paraposition, for example, a compound of the general formula wherein R may stand for a benzene or naphthalene radical containing a hydrogen atom in para position to the nitrogen atom, A and A may stand for identical or different, substituted or unsubstituted aliphatic groups, containing at the most four and preferably up to two carbon atoms in the aliphatic groups. Any substituents if present should be free from ionogenic properties.

Thus for example A and A may be benzyl groups or A may be a methyl group and A a formyl group.

A particularly useful group of starting materials are those corresponding to Formula 1, in which R is a benzene residue containing a hydrogen atom in paraposition to the nitrogen atom and A and A are alkyl group which may be substituted, or N, A and A together form a heterocyclic ring. Hydroxyl, alkoxy and cyano groups may be mentioned as examples of substituents in the alkyl group A; and/or A The'alkyl groups advantageously contain only few carbon atoms, as in the case of ethyl and methyl groups. Substituents, for example, halogen atoms or alkyl or alkoxy groups, may be present in the benzene residue R in orthoor meta-position to the dialkyl amino group, which may itself contain substituents, or the benzene residue may be free from further substituents, in which case the aminoaryl compound is of the general formula in which the two carbon atoms of the heterocyclic fivemembered ring are connected by double bond (indoles) or a single bond (indolines).

Among the indoles those unsubstituted in the 3-position there may be mentioned indole, Z-phenylindole, 1- methyl 2 phenylindole, 1-methyl-2-phenyl-6-nitroindole and 1:2-dimethylindole. In the process of this invention an aldehyde group is introduced into the 3-position of these compounds.

It is especially advantageous to introduce an aldehyde group into the H C-group in the 2-position of an N- substituted 3:3-dialkyl-Z-methylene-indoline, especially a 1:3:3-trialkyl-2-methylene indoline. These compounds may be substituted at the nitrogen atom (in l-position), for example, by a benzyl group or another alkyl group, and the following compounds may be mentioned as examples, 1:3 3-trimethyl-2-methylene-indoline, 1 :3 :3-triethyl-Z-methylene-indoline, l-benzyl 3:3 dimethyl-Z- methylene indoline, l:3:3-tributyl-2-methylene-indoline, 1:3:3-trimethyl methoxy 2 methylene-indoline, 1:3:3-trimethyl 5 chloro Z-methylene-indoline, 113:3- trimethyl-2-methylene-indoline 5 carboxylic acid ethyl ester, and 4:5 benzo 1:3:3 trimethyl 2 methyleneindoline.

Furthermore it is possible to introduce an aldehyde group in 4-position of a pyrazolone(5) ring especially a 1-phenyl-3-methyl-pyrazolone(5).

In carrying out the process of this invention it is not necessary to separate the dichloro-{dialkylamino)-methane from the reaction mixture in which it was made. As a rule it is of advantage to add the compound, into which an aldehyde group is to be introduced, to the above mixture when the reaction between the dialkylformamide and phosgene is finished. Due to the good reactivity of dichloro (dialkylamino) methane the condensation starts immediately. For the purpose of obtaining a final product having a high degree of purity and in good yield the whole of the compound containing a reactive hydrogen atom should not be added at once, but gradually, and care should be taken that the reaction temperature does not rise too much, for example, not above 20 C., before the combination of the reaction components is complete. Subsequently the temperature may be raised, for example, to 50 to 70 C. to complete the reaction. During the condensation the components combine with one another in equimolecular proportions and one molecular proportion of hydrogen chloride is split off, for example, in accordance with the following equation:

A CH3 The condensation product so obtained is treated with a hydrolyzing agent. For this purpose the reaction mixture, containing the condensation product, may be mixed with ice or ice-water, whereupon the condensation product generally first dissolves in the water and the splitting to form the aldehyde occurs subsequently. Alternatively the hydrolysis may be brought about by the addition of 4 alkali, for example, an alkali metal hydroxide. The hydrolysis may be represented as follows:

A, 01 CH;

NN H10 Aa Iii CHs A{\ (II) /CII3 No in: 1101 AZ 1i cn,

From the hydrochloride of the amino-aldehyde obtained by the action of water and usually dissolved in the water, the free base can be obtained in the usual manner by means of an alkali.

Many of the aldehydes which can be made according to the present process are known products for which there is a constant industrial demand.

As stated above, aldehydes are obtained by the process of this invention in good to very good yields and in a very advantageous manner. In this respect the process is superiod to the known process described in German specification No. 677,207, in which an indole arylated or alkylated in the 2-position and unsubstituted in the 3-position, or an N-substituted indole containing in the 2-position a reactive methylene group and in the 3-position two alkyl groups, is reacted with a condensation product of phosgene with an N-formyl-compound of a secondary aromatic amine.

The following examples illustrate the invention, the parts and percentages being by weight unless otherwise stated and the relationship of parts by weight to parts by volume being the same as that of the kilogram to the liter.

Example 1 parts of phosgene were introduced at a temperature of 10 to 20 C. into a solution of 40 parts of dimethylformamide in 400 parts by volume of carbon tetrachloride, the solution being slightly cooled. Carbon dioxide was released, and dimethylamino-dichloromethane was formed, and was precipitated as a white crystalline mass practically insoluble in carbon tetrachloride. When the whole phosgene had been introduced stirring was continued, until phosgene Was no longer detectable, this being the case after about 30 minutes. The crystalline paste was then cooled to 10 C., and parts by weight of N-methyl-N-fi-cyanoethylaminobenzene were added dropwise. A bright yellow compound was gradually formed which probably has the general formula The mixture was stirred for one half hour at a temperature of 10 to 20 C., and to complete the reaction was slowly heated to a temperature of 50 to 55 C. At this temperature the yellow precipitated compound, insoluble in carbon tetrachloride melted to a yellowish brown, oily mass which after some time solidified to a bright yellow crumbly mass. The whole mixture was kept for 3 to 4 hours at a temperature of 50 to 55 C., and then it was poured into 800 parts of ice with 200 parts of water, the yellow aldehyde dissolving in the water, and the clear carbon tetrachloride, which collected at the bottom, was separated quantitatively. The aqueous solution having an acid reaction to Congo was neutralized, while stirring well, by slowly introducing to parts of a sodium hydroxide solution of 30 percent strength until addition of sodium hydroxide ceased to produce a whitish precipitate. The temperature was kept at about 15 and the pH value at 8 to 9. The separated corresponding to about 90 percent of the theoretical value, and its melting point was 68 to 71 C.

In the following table are given in column II the chemical formulae and color of aldehydes which have been made by the procedure described above from the reaction product of phosgene and dimethylformamide and the amines given in column I.

I V II III IV Tertiary amine (starting material) Aldehyde (final product) Melting Yield,

point of II percent 1 /N /N- -CHO 72 to 73. 90 to 95 (bright yellow) s 2\ HaCz 2 0 5 (yellow-brown) H O H;C\ 3 /N= /N CHO to H30 H30 M (yellow-brown) Hfic2\ H502 4 ,N

H 0 H O;

OCzH5 0-CzH5 (dark brown) 5 /N /N -CHO l1q111d.. 90

H3C-0C2H4 H3C00ZH3 HOC2H4 HOC2H4 6 /N /N OHO d0 75 Noolrn NOO H H5Ca\ 5 2 7 NQ N OH0 do 95 H5Cz H503 CH3 CH3 (yellow-brown) H502 H5Cg\ 8 N N -OHO 60 OH OH 9 N /N CHO liquid 81 HO HE") ll 0 (yellow-brown) n t? i 10 2C\ l (IT l 86 (\}=1\: 0 (3: CH CH (yellow) 11 NQ /N -0H0 9s Oar: H2O

(yellow) I II III IV Tertiary amine (starting material) Aldehyde (final product) Melting Yield,

point of II percent CH; CH;

(yellow-brown) 11 C H C\ 13 N /N CI'IO do 86 (yellow-brown) OH /CH\ 14 HN on IIN o orro 81 It is to be understood that the yield given in column IV is not the maximum yield obtainable by carefully looking for the best operating conditions but mostly the yield obtained in one trial on a laboratory scale.

Example 2 50 parts of phosgene were introduced at to C. into a mixture of 400 parts by volume of carbon tetrachloride and 41 parts of dimethylformamide. When phosgene could no longer be detected 86.5 parts of l:3:3-trimethyl-2-methylene-indoline at 5 to 15 C. were slowly added. After stirring for about 2 hours, the temperature was slowly raised to about 40 to 50 C. If the heating is too rapid the reaction temperature will quickly rise to 60 C. with the formation of lumps. After 3 hours the reaction mass was poured, while stirring well, into 100 parts of ice and water, and the carbon tetrachloride layer was allowed to settle and was then separated. The aqueous layer was rendered alkaline with 130 parts of sodium hydroxide of percent strength, whereby the aldehyde was hydrolysed with the splitting off of dimethylamine, which was removed by distillation with steam. Upon cooling, the aldehyde of the formula separated as a bright yellowish brown crumbly mass. The yield of the aldehyde melting at 112 to 115 C. was about 95 parts, corresponding to about 95 percent of the theoretical value.

The following examples illustrate slightly different procedural steps for products mentioned in the table of Example 1.

Example 3 Into a solution consisting of parts of dimethylformamide and 600 parts of carbon tetrachloride which had been freed from traces of water, 51 parts of phosgene were introduced at 0 C. When no phosgene could be detected 89.5 parts of N-ethyl-N-methoxyethylamino benzene were added dropwise but fairly quickly. After /2 hour the mixture was heated to -55 C. and kept for 6 hours at that temperature. Then the whole was left to cool without stirring, the carbon tetrachloride was removed from the bottom and the residue was dissolved in water with the addition of ice. Sodium hydroxide solution was added until a distinctly alkaline reaction to mimosa paper was obtained, and the mixture was distilled with steam for a short time. Then the liquid aldehyde was separated from the supernatant water, washed with cold water and dehydrated in vacuo. The yield was 93 parts of 4-(N-ethyl-N-methoxyethylamino)benzaldehyde( 1 Example 4 To a suspension in 640 parts of carbon tetrachloride of the dimethylamino-dichloro-methane formed from 40 parts of dimethylforrnamide and 51 parts of phosgene kept at 510 C., 61 parts of ILN-dimethylaniline were added slowly and while stirring well. Then the temperature was raised carefully to 45-50 C. and was kept several hours at that value. Then the carbon tetrachloride was slowly distilled off. The residue was dissolved in Water with the addition of ice. First a clear solution was formed and afterwards hydrolysis occurred, and dimethylamino benzaldehyde separated out. The mixture was rendered alkaline and subjected to a steam distillation for a short time. After cooling down the mixture, the aldehyde was separated as a white precipitate in a yield of 63 parts and with a melting point of 70-73 C.

Example 5 50 parts of phosgene were introduced into a solution of 40 parts of dimethyl formamide in 600 parts of trichloroethylene kept at 0 C. Then 74.5 parts of diethylaniline were added at 10 C. dropwise but fairly quickly. After the reaction was finished the whole was heated to 70 C. and after some hours the trichloroethylene was removed from the bottom. The residue was dissolved in water with the addition of ice, parts of a 30 percent sodium hydroxide solution were added and the mixture was distilled with steam for a short time. The resulting N,Ndiethyl aminobenzaldehyde was obtained as an oil in almost quantitative yield.

What is claimed is:

1. Dichloro-dialkylamino-methane wherein each alkyl is lower alkyl containing at most two carbon atoms.

2. Dichloro-dimethylamino-methane.

3. Dichloro-diethylamino-rnethane.

References Cited in the file of this patent FOREIGN PATENTS Germany June 21, 1939 OTHER REFERENCES 

1. DICHLORO-DIALKYLAMINO-METHANE WHEREIN EACH ALKYL IS LOWER ALKYL CONTAINING AT MOST TWO CARBON ATOMS. 